Involatile materials and materials with low volatility are difficult to analyze by mass spectrometry because it is necessary to vaporize the materials prior to ionization. Materials that are thermally stable may be heated to increase their volatility. Unfortunately, molecules of biological origin, such as peptides, decompose when heated. One technique for producing molecular ions from such molecules comprises irradiating a solution or dispersion of the analyte molecules with a primary particle beam composed of ions (secondary-ion mass spectrometry or SIMS) or atoms (fast atom bombardment or FAB).
The SIMS and FAB techniques produce ions not only of the analyte but also of the matrix (the solvent or liquid carrier) in which the analyte is dissolved or dispersed. This produces a background spectrum that effectively limits the sensitivity of the experiment. For example, the detection limit for the peptide Eledoisin (molecular weight equals 1187 daltons) when dispersed in a glycerol matrix and analyzed by normal FAB techniques is in the range of one to ten picomoles (1 picomole=10.sup.-12 mole). At lower quantities this molecular species [M+H]+ cannot be distinguished from the background spectrum evolved from the matrix in which the analyte is dispersed or dissolved.
It has been known for some time by the applicants and others that the rates at which analyte ions and matrix ions are formed immediately following initiation of primary particle beam bombardment are often different. This phenomenon is documented, for example, in Musselman et al. "Differential Appearance of Analyte and Matrix During the First Seconds of Sputtering by Fast Atom Bombardment," a paper presented at the 35th ASMS Conference on Mass Spectrometry and Allied Topics (Denver, Co., May, 1987). This phenomenon, while known, has never been suggested as the basis of an improved mass spectrometry analyte ion generation technique.
Several FAB mass spectrometry techniques make use of ion pulses but only for special cases such as time-of-flight (TOF) spectrometers and Fourier transform mass spectrometry. See, for example, Shabanowitz et al. "Tandem Quadrupole-Fourier Transform Mass Spectrometry: New Developments," presented at the 34th Annual Conference on Mass Spectrometry and Allied Topics, (Cincinnati, Ohio, June, 1986); Olthoff et al. "Desorption Mechanisms Using A New Liquid-SIMS-TOF Mass Spectrometer," a paper presented at the 35th ASMS Conference on Mass Spectrometry and Allied Topics (Denver, Co., May, 1987); Chen et al. "Design and Performance of a Continuous Flow Probe HPLC Interface for a Liquid SIMS Time-of-Flight Mass Spectrometer," a paper presented at the 36th ASMS Conference on Mass Spectrometry and Allied Topics (San Francisco, Calif., June, 1988); Olthoff et al. "Liquid Secondary Ion Time-of-Flight Mass Spectrometry," Analytical Chemistry, Vol. 59, No. 7 (April, 1987).
The applicants are aware of no pulsed technique for dramatically increasing the sensitivity of the FAB or SIMS experiments using a conventional double-focussing mass spectrometer.